A better understanding of the pathophysiology of the acquired immune deficiency syndrome (AIDS) and the development of both antiviral treatment modalities and an efficacious vaccine for this disease are needed to control the current epidemic. Achieving these goals will be greatly facilitated by the development and exploitation of an animal model for AIDS. The only animal species which has been shown to be infectable with HTLV-III/LAV, the etiologic agent in AIDS, is thee chimpanzee. However, the chimpanzees have developed no signs of disease following infection with HTLV-III/LAV. This finding, as well as their endangered status, lack of ready availability and cost, make the use of the chimpanzee in AIDS research problematic. In the studies, a naturally occurring immunodeficiency syndrome of macaque monkeys with striking parallels to human AIDS has been defined. Its clinical and pathologic characteristics have been described, its transmissibility with tissue from affected animals has been demonstrated and a type C retrovirus has been isolated from these animals. This virus, STLV-III, is morphologically indistinguishable from and antigenically related to HTLV-III/LAV. STLV-III, upon inoculation into healthy juvenile rhesus monkeys, induces a disease characterized by immunologic dysfunction, including a decrease in T4+ PBL, and death due to wasting, opportunistic infections and primary retroviral enchephalitis. The work will further develop this AIDS model in macaque monkeys and exploit it to elucidate further the pathophysiology of AIDS. The experiments described include the characterization of the immune response to STLV-III, the characterization of events in the pathogenesis of STLV-III induced disease in macaque monkeys and the definition of variables in the STLV-III/macaque model.